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Type: Artigo de periódico
Title: Signalling pathways regulating human neutrophil migration induced by secretory phospholipases A(2)
Author: Gambero, A
Thomazzi, SM
Cintra, ACO
Landucci, ECT
De Nucci, G
Antunes, E
Abstract: This study was designed to elucidate the signalling pathways by which secretory phospholipases A(2) (sPLA(2)s) induce in vitro neutrophil migration. The cell migration assays were performed with Naja mocambique venom PLA(2) (sPLA(2) with high catalytic activity), bothropstoxin-I (sPLA2 devoid of catalytic activity) and platelet-activating factor (PAF), using a 48-well microchemotaxis chamber. Both the non-selective protein kinase inhibitor staurosporine (30-300 nM) and the selective protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpyperazine (H7; 50-200 muM) as well as the Gi inactivator pertussis toxin (30-300 nM) caused a concentration-dependent inhibition of the neutrophil migration induced by either N. mocambique venom PLA(2) (100 mug/ml) or bothropstoxin-I (100 mug/ml). Pertussis toxin nearly abolished PAF-induced migration, while staurosporine and H7 partly (but significantly) inhibited the chemotactic responses to PAR The dual inhibitor of cytosolic PLA(2) and Ca2+-independent PLA(2) (iPLA(2)), arachidonil-trifluoromethyl-ketone (ATK; 0.2-20 muM), or the specific iPLA(2) inhibitor bromoenol lactone (1-30 muM) caused a concentration-dependent inhibition of the migration induced by either sPLA(2)s. At the maximal concentration used for each compound, the migration was almost suppressed. In contrast, both of these compounds caused only slight inhibitions of PAF-induced migration. No rise in intracellular Ca2+ Was observed in neutrophil-stimulated sPLA(2), as determined in cells preloaded with fura 2-AM. In the experimental condition used, pertussis toxin, staurosporine, H7, ATK or bromoenol lactone did not induce cytotoxic effects, according to MTT assay. Our results suggest that activation of an endogenous PLA(2) through activation of GTP-binding protein and PKC is the main mechanism by which exogenous sPLA(2)s cause neutrophil migration. (C) 2004 Elsevier Ltd. All rights reserved.
Subject: phospholipase A(2)
neutrophil migration
protein kinase C
intracellular Ca2+
Country: Inglaterra
Editor: Pergamon-elsevier Science Ltd
Rights: fechado
Identifier DOI: 10.1016/j.toxicon.2004.06.004
Date Issue: 2004
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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